The objective of this Program Project is the multidisciplinary study of the etiology of gastric cancer, focused on premalignant lesions. The current cycle is based on findings of the previous funding cycles which have led to the postulation and refinement of an etiologic model. The first project is the continuation of a chemoprevention trial designed to determine the efficacy of antioxidant supplementation (ascorbic acid and/or beta carotene) and/or anti-Helicobacter pylori treatment in retarding the progression of the premalignant process. The second project provides an evaluation of the histological and molecular endpoints used in all the other components of the program. All of the proposed studies are closely interrelated and complementary. They explore the mechanisms of action of the factors involved in the gastric precancerous process and its possible inhibition. These studies have the potential to provide important new knowledge about gastric carcinogenesis and to contribute to the goal of primary prevention of this common cancer.